Subproject 2 will be a direct extension of our ongoing work and will develop objective and quantitative criteria for classifying mild cognitive impairment (MCI) in adults with Down Syndrome (DS) based upon the assessment methods we have been employing in our current studies. Alzheimer's disease (AD) in adults with DS represents a very real and highly significant public health concern. The current increase in the number of aged individuals with DS warrants dependable strategies to improve early detection of cognitive impairment and for identifying individuals at high risk for developing frank dementia. There is increasing evidence that subtle losses in cognitive functions may be symptomatic of a transition to early AD. This suggests that we may be able to identify such individuals prospectively and as therapeutic interventions become available, clinicians can intervene to halt or slow the progress towards severe dementia. The construct of Mild Cognitive Impairment (MCI) has been used to describe this intermediate state between cognitively normal aging and dementia. Identifying MCI in adults with DS can be difficult because of their lifelong cognitive deficits and variability in baseline level-of-functioning. Despite these difficulties, recent longitudinal studies have shown that measures of memory and other cognitive functions that are appropriate for use with adults with DS are sensitive to relatively subtle decline. Recent research also suggests that neuropsychiatric symptomatology may be indicative of MCI and may predict progression to AD. Based upon a substantial body of data collected during our current funding period, we have generated sets of criteria referenced to baseline IQ that appear to differentiate cognitively normal individuals and those exhibiting MCI with moderately good sensitivity and specificity. However, because these criteria have been generated from our obtained data, original estimates of their accuracy may be overly optimistic. We now need to confirm that our methods are valid and that they have prognostic value. We are confident that this validation will prove successful. We will then have a cognitive and functional assessment battery with standardized procedures and objective classification criteria that can inform clinical judgment regarding whether an individual with DS is showing declines in functioning that are consistent with current conceptions of MCI.